BACKGROUND: With present day treatment, radiation and surgery are capable of curing approximately 50 percent of cancer patients; consequently, effective chemotherapy applicable to most or all cases of neoplastic diseases is urgently needed. Chemotherapy has already shown encouraging progress in the treatment of choriocarcinoma, Burkitt's lymphoma, certain other types of lymphomas and juvenile leukemias, Hodgkin's disease and certain endocrine tumors. However, in the great majority of solid tumors and adult onset leukemias and especially brain tumors, chemotherapeutic efforts so far have failed to produce lasting results and there is a great deal to be achieved in the rational design of chemotherapy for cancer and allied diseases. THE AIM OF THIS RESEARCH PROGRAM: (1) The objective of this investigation is to elucidate strategic exploitable metabolic, enzymatic and isozymic differences between normal and neoplastic tissues of different growth rates and differentiation to provide a molecular basis for a rationally planned selective chemotherapeutic approach. (2) A thorough understanding of the main differences between normal and cancerous tissues at the molecular level should permit the evaluation of the regulatory mechanisms of gene expression which play crucial roles in the differentiation, replication and functioning of normal and neoplastic cells. It is expected that an elucidation of the enzymatic basis of the key metabolic and regulatory alterations in cancerous tissues and an understanding of the factors which govern the pattern of gene expression might permit the design of new drugs and approaches to control neoplastic diseases by chemotherapy. (3) The ultimate goal of this program is to identify key metabolic, enzymatic, and isozymic targets for chemotherapy and to develop chemical compounds possessing a high degree of selective toxicity to cancer cells in order to achieve lasting chemotherapeutic results. BIBLIOGRAPHIC REFERENCES: G. WEBER, N. PRAJDA AND R. C. JACKSON: Key Enzymes of IMP metabolism: transformation- and proliferation-linked alterations in gene experssion. Advances in Enzyme Regulation 14, 3-24 (1976). G. WEBER, R. C. JACKSON AND N. PRAJDA: Enzymatic markers of malignant transformation. Pro. Am. Assoc. Cancer Res. 17, 43 (1976).